Preparation of civetone and its homologs



United States Patent PREPARATION OF CIVETONE AND ITS HOMOLOGS Alfred T.Blomquist, and Joseph Wolinsky, Ithaca, N. Y.

No Drawing. Application December 9, 1955, SerialNo. 552,228

6 Claims. (Cl. 260-586) This invention relates .to the production ofchemicals and in particular to the production of large-ring ormacrocyclic-monoketones.

A- principal object of the present inventionis to provide a process forthe production of-ho'mol'ogs of civetone from symmetrical macrocyclicdiketones.

Another object of the invention is to provide a process for theproduction of S-cycloliexadecen-l-one from 1,9- cyclohexadecanedione.

Still another object of the invention is to'provide a process for theproduction: of 9-cyclooctadeeen-1-one from 1,l O cyclooctadec'anedione.

Other objects of? the invention will in part be obvious and will in-partappear-hereinafter.

The invention accordingly comprises the process involving the severalsteps and the relation and the order of one or more of such stepswith.respect to each of the others which are exemplified in the followingdetailed disclosure, and the scope of the application of which isindicated in the claims.

Fora fuller, understanding of. the nature and objects of the invention,reference should. be had to the following detailed description.

Civetone. or 9-cycloheptadecen-l-one: of the following structure is anaturally occurring substance secreted by the civet cat. exceptionalvalue to the perfume industry as a. perfume base and fixative.Homol'ogs. of civetone having from 14 to 18 ring members also possess amusk-like odor very similar to that of the naturally occurring civetone.Although there are described in Chemistry of; Carbon Compounds, E. Rodd,ed., New York,,Elsevier Publishing. Company, 1953, volume. II, part A,pages. 277- 284, several syntheses for the. perfumery fixativecivetone,

little attention has been given to.the.synt1hesi s of civetone homologssuch as 7-cyclotetradecen-l-one, 8-cyclohexadecen-l-one and9-cyclooctadecen-l-one. One method for producing these civetonehomologs, described. in

Swiss Patent 135,921. 1928)v and U. S. Patent 1,873,154,.

Due to its characteristic musk-like odor, it is. of

ketone. In one preferred embodiment of the invention, the reactionproceeds as follows:

2) CH(0H2) n-1 -n o l noon 1'0 I 00 where n and n are whole numbers offrom 6 to 8 and where n and n, are numerically equal. In anotherembodiment, the preferred symmetrical macrocyclic diketones are1,9-cyc1ohexadecanedione. and l,l0-cyclooctadecanedione, and thecivet'one homologs. produced therefrom are 8 cyclohexadecen-l-one and9-cyclooctadecenl-one respectively. The symmetrical macrocyclicdiketones employed as starting materialin the present invention may beprepared accordingto the methods described in U. S. Patent 2,584,664.

Specific detailed methods of practicing the present invention are setforth in the following non-limiting examples.-

Example I An acetic acid solution of 0.503 gramofl,9-cyclohexadecanedione was hydrogenated in a semi-micro apparatus,using 70 milligrams of prereduced Adams catalyst (finely dividedplatinum. produced. by the reductionof platinum oxide), until, about1.04 percent of one. equivalent of. hydrogcn had been absorbed. Afterseparation, of the catalyst andreinoval. of. the acetic acid. invacuo,the residual solid was treated, with about 60 milliliters of hexane atroom temperature. There was obtained 0.07 grain of crude1,9-cycl0hexadecanediol which was insoluble in hexane. Coolingthefiltered hexane solution to 0-5 C.

1 gave 0.22 gram of 9-hydroxycyclohexadecanone. The remaining hexanesolution was then. placed on on a magnesol-celi-te column. Elution witha pentane-benzene mixture gave 0.09 gram of the starting material,1,9-cyclohexadecanedione. Elution with a chloroform-benzene mixture gavean additional 0.09 gram oi 9-hydroxycyclohexadecanone as fine fluflfyneedles. After recrystallization, the cyclic hydroxyketone obtained hada melting point of 7677 C. The'total quantity of 0.31 gram of'9-hydroxycyclohexadecanone produced represented a 61 percent yield.

The above reaction proceeded as follows:

Arnixture of. 170 milligrams of 9-hydroxycyclohexadecanone and 1.5 gramsof potassium hydrogen sulfate was heated for about 5 minutes at about250 C. The resulting mixture was cooled and extracted with pentane.Evaporation of the pentane solution gave a residual oil having. anintense musk odor. On cooling, this liquid solidified. About 145milligrams of 8.-cyclohexadecen-lone with a melting point of 1'7'-22 C.were obtained. This represented a yield of about. percent.

The above reaction proceeded as follows:

An acetic acid solution of 0.81 gram of 1,10-cyclohexadecanedione waspartially hydrogenated using the procedure described in Example I. Afterseparation of the catalyst and removal of the acetic acid, the residuewas dissolved in hexane and placed on an alumina column. Elution with ahexane-heptane mixture gave 0.23 gram of unreduced1,IO-cyclohexadecanedione. Elution with a hexane-benzene mixture gave0.23 gram of 10- hydroxycyclooctadecanone. Final elution with chloroformalso gave 0.16 gram of 1,10-cyclooctadecanediol. After recrystallizationfrom pentane, the cyclic hydroxyketone obtained had a melting point of80-81 C.

The above reaction proceeded as follows:

CO HOCH 155 milligrams of -hydroxycyclooctadecanone were fused with 2grams of potassium hydrogen sulfate using the procedure described inExample I. Crude 9-cyclooctadecen-l-one was obtained directly from thefused mixture by sublimation. After resublimation, 95 milligrams of9-cyclooctadecen-1-one were obtained as a Waxy solid with a meltingpoint of 4041 C. This material had a musk odor similar to that ofcyclooctadecanone. The total quantity of 9-cyclooctadecen-1-one obtainedrepresented a yield of 66 percent.

This reaction proceeded as follows:

The above process is also applicable to the production of7-cyclotetradecen-l-one from 1,8-cyclotetradecanedione.

The partial reduction of the symmetrical macrocyclic diketones havingfrom 14 to 18 ring members (12 to 16 methylene groups between the ketogroups) may be achieved in many alternative ways other than through theuse of Adams catalyst in acetic acid. For example, Raney nickel,palladium on charcoal, nickel on kieselguhr, copper chromite, platinumor palladium on various other Well-known supports may also be used ascatalysts. The above catalysts are used typically in solvents such asethanol, ethyl acetate, acetic acid and the like.

Conditions of reaction such as temperature, pressure, use of solvents,etc., depend on the particular hydrogenation method employed. Thehydrogenation must be closely controlled so that but one ketonc group ofthe cyclic diketone employed is reduced to a secondary alcoholicgrouping. Complete hydrogenation of the cyclic diketone is undesirablesince it produces cyclic diols. For instance, the complete hydrogenationof 1,9-cyclohexadecanedione or 1,10-cyclooctadecanedione results in1,9-cyclohexadecanediol and 1,10-cyclooctadecanediol respectively.

The partial reduction of the preferred diketones results in symmetricalhydroxyketones having the same number of ring members as the startingmaterial from which it was produced. Thus the number of methylene groups(CH2) between the hydroxy group and keto group of the hydroxyketone areequal to the number of methylene groups between the two keto groups ofthe starting material.

The dehydration of the symmetrical macrocyclic hydroxyketone may also beachieved by additional methods other than through the use of potassiumhydrogen sulfate. For example, the dehydration may be accomplished byheating the hydroxyketone with sulfuric, phosphoric, formic, oxalic orsulfonic acids or with reagents such as fused zinc chloride, iodine andthe like or by passing the vapors of the hydroxyketones over substancessuch as alumina, thoria, titania, aluminum silicates and the like atsuitable temperatures. Conditions of reaction for the dehydration suchas temperatures, use of solvents and the like depend upon the particulardehydration method employed.

The dehydration of the preferred hydroxyketones results in unsymmetricalunsaturated monoketones which, however, contain the same number of ringmembers as the diketone and hydroxyltetone from which they are obtained.The preferred macrocyclic unsaturated monoltetones, having from 14 to 18ring members but containing one less methylene group between thefunctional groups than are present between the functional groups of thesymmetrical cyclic diketone or hydroxyketone, possess the valuable muskodor.

Although specific separation techniques were illustrated in theexamples, it should be pointed out that the use of other solvents andseparation techniques may be employed in the recovery of either thehydroxyketone or the unsaturated monoketone.

Since certain changes may be made in the above process without departingfrom the scope of the invention herein involved, it is intended that allmatter contained in the above description shall be interpreted asillustrative and not in a limiting sense.

What is claimed is:

1. A process for the production of civetone homologs which comprises thesteps of partially reducing a symmetrical macrocyclic diketone selectedfrom the group consisting of 1,S-cyclotetradecanedione,1,9cyclohexadecanedione and 1,10-cyclooctadecanedione to thecorresponding symmetrical macrocyclic hydroxyketone and dehydrating saidsymmetrical macrocyclic hydroxyketone to a macrocyclic unsaturatedmonoketone of the general formula where n and n are whole numbers offrom 6 to 8 and where n and n are numerically equal.

2. A process for the production of civetone homologs which comprises thesteps of partially reducing 1,9-cyclohexadecanedione to9-hydroxycyclohexadecanone and dehydrating said9-hydroxycyclohexadecanone to S-cyclohexadecen-l-one.

3. A process for the production of civetone homologs which comprises thesteps of partially reducing 1,10- cyclooctadecanedione to10-hydroxycyclooctadecanone and dehydrating saidlO-hydroxycyclooctadecanone to 9-cyclo0ctadecen-1-one.

4. A process for the production of civetone homologs which comprises thesteps of partially reducing 1,8-cyclotetradecanedione to8-hydroxycyclotetradecanone and dehydrating said8-hydroxycyclotetradecanone to 7-cyclotetradecen-l-one.

5. A process for the production of macrocyclic unsaturated monoketoneswhich comprises the steps of partially reducing a macrocyclic diketoneto the corresponding macrocyclic hydroxyketone and dehydrating saidmacrocyclic hydroxyketone to a macrocyclic unsaturated monoketone havingone less methylene group between the unsaturation and keto group than ispresent between the keto groups of said macrocyclic diketone.

6. A process for the production of macrocyclic unsaturated monoketoneswhich comprises the steps of partially reducing a symmetricalmacrocyclic diketone to the corresponding symmetrical macrocyclichydroxyketone and dehydrating said symmetrical macrocyclic hydroxy-'ketone to an unsymmetrical macrocyclic unsaturated monoketone.

- No references cited.

1. A PROCESS FOR THE PRODUCTION OF CIVETONE HOMOLOGS WHICH COMPRISES THESTEPS OF PARTIALLY REDUCING A SYMMETRICAL MACROCYLIC DIKETONE SELECTEDFROM THE GROUP CONSISTING OF 1,8-CYCLOTETRADECANEDIONE,1,9-CYCLOHEXADECANEDIONE AND 1,10-CYCLOOCATDECANEDIONE TO THECORRESPONDING SYMMETRICAL MARCROCYLIC HYDROXYKETONE AND DEHYDRATING SAIDSYMMETRICAL MACROCYLIC HYDROXYKETONE TO A MACROCYCLIC UNSATURATEDMONOKETONE OF THE GENERAL FORMULA